The goal of our research is to provide an understanding of the mechanisms of expression and regulation of mouse heavy chain immunoglobulin genes. We are mainly focusing our attention on the molecular basis of the heavy chain constant region gene (CH) switch. This phenomenon would appear to involve DNA rearrangement events mediated via homologous recombinations occurring within tandemly repetitious DNA sequences (S region). These sequences are located within approximately 2 Kbp 5' of the CH genes. We are exploring the genetic properties of CH gene S sequences in a variety of inbred mouse strains and wild mice. These sequences appear to be intrinsically unstable in the mouse germ line and also exhibit extensive sequence divergence between different mouse species. Experiments on functionally and nonfunctionally rearranged CH genes in mouse myelomas have demonstrated that CH gene switches are not always productive and may indeed be a random process.